The present invention relates generally to proteins which bind Interleukin-4 and, more specifically, to compositions containing isolated Interleukin-4 binding proteins.
Interleukin-4 (IL-4) is one of many cytokines which regulate the function of immune cells. IL-4 has broad effects on B cells, such as enhancing the secretion of IgE and IgG.sub.1 isotypes in activated B cells. In addition, IL-4 promotes the proliferation and differentiation of T lymphocytes, as well as a wide range of hematopoietic cell lineages. IL-4 mediates its effects by binding to cell surface receptors and initiating a complex series of events within the responsive cell. Cloning of the murine and human IL-4 receptors have recently been reported by Mosley et al., Cell 59:335 (1989) and Idzerda et al., J. Exp. Med. 171:861 (1990).
The immune system can malfunction, resulting in autoimmune diseases such as arthritis, diabetes, allergy and asthma. In some instances normal immune responses are also undesirable, such as when the immune system attacks and causes rejection of transplanted organs. IL-4 has been shown to play a specific role in activating immune cells to produce antibodies responsible for allergic and asthmatic reactions, and to attack transplanted tissue. Mosely et al. (supra) identified naturally occurring soluble forms of the IL-4 receptor consisting of the extracellular region of the receptor and which function as IL-4 antagonists by binding to IL-4, thus preventing IL-4 from binding to a cell surface receptor and transducing an IL-4 biological signal. Such IL-4 antagonists may be of clinical use in inhibiting IL-4 mediated immune responses, for example in alleviating or preventing IgE-induced allergic responses or rejection of transplanted tissue.
A specie of IL-4 antagonist has recently been isolated from human urine using an IL-4 affinity column. This IL-4 antagonist, designated IL-4 binding protein-.beta. or IL-4bp.beta., is unique, having an N-terminal amino acid sequence distinct from human or murine IL-4 receptor. IL-4bp.beta. is described in detail in copending U.S. patent application Ser. No. 07/667,687, filed Mar. 8, 1991.
The present invention provides yet another distinct specie of IL-4 antagonist which is referred to as Interleukin-4 Binding Protein-.gamma., or IL-4bp.gamma.. The N-terminal amino acid sequence of IL-4bp.gamma. indicates that this protein is distinct from IL-4bp.beta. and from murine and human IL-4 receptors.